This invention relates to compositions and methods for modulating nutrient partitioning. More particularly, the present invention provides a composition and a method for modulating nutrient partitioning in humans so as to normalize nutrient pathways which play a key role in numerous metabolic disorders, the composition and method being designed to prevent, delay or reverse such disorders.
Disorders of nutrient partitioning leading to biochemical signaling abnormalities form the basis for a group of metabolic disorders. These include but are not limited to insulin resistance, hyperinsulinemia, Syndrome X, hypertriglyceridemia and/or low HDL syndrome, high RQ (respiratory quotient) syndrome, obesity, chronic fatigue syndrome, small dense LDL syndrome, recidivism from weight loss, glucolipoxia, premature aging, memory loss, endothelial dysfunction, vascular disease, hypertension, postprandial hyperlipidemia, certain types of cancer, metabolic inflexibility and others. The basic abnormality is similar in each circumstance but manifests clinically in different ways depending upon the organ involved, the individual""s genetic makeup, age, sex and other factors.
The two major macronutrient fuels are fat and carbohydrate (which is stored in the body as glycogen). In the body, fat and carbohydrate are combined in certain proportions to generate the fuel mix the body burns at any point in time. If the fuel mix contains more carbohydrate, it contains relatively less fat and vice versa. Because there is minimal metabolic transformation between carbohydrate and fat, if more fat is being burned, then less is being stored and vice versa. The same holds true for carbohydrate, i.e., if more carbohydrate is being burned, then less is being stored and vice versa.
The relative ratio of fat and carbohydrate contributing to the fat/carbohydrate fuel mix is referred to as the xe2x80x9crespiratory quotientxe2x80x9d (RQ). RQ is approximately 1 when only carbohydrate is being burned and is about 0.8 when fat is the sole component being oxidized. A mixture of fuels is assigned a number between approximately 0.8 and 1.0. The nutrient partitioning abnormality most frequently encountered as manifested by an elevated RQ indicates excessive fat storage associated with excessive combustion of carbohydrate. This condition predisposes to increased intracellular lipid stores in numerous organ systems as well as the entire body. The most affected organs are the liver, pancreas, adipose tissue and skeletal muscle. Also involved is the hypothalamic-pituitary-adrenal axis as well as the vascular wall. When lipid stores accumulate in these organs, they produce alterations in intracellular signaling systems including insulin and protein kinase C (PKC) signaling pathways leading to skeletal muscle insulin resistance, excessive basal insulin secretion by the pancreas associated with a decrement in glucose-induced insulin release, an impairment of insulin action at the level of the liver manifested by decreased sensitivity of insulin suppression of hepatic glucose output, expansion of (visceral) fat stores, excessive cortisol secretion and endothelial dysfunction associated with altered nitric oxide physiology. The defects primarily involving insulin signaling pathways act as predisposing factors which increase tissue glycation and oxidative stress. This constellation of abnormalities combines in various ways to form the basis for the metabolic diseases mentioned above.
For various reasons, approximately 30% to 50% of the population of westernized societies manifest overtly abnormal fuel homeostasis. As a result, affected individuals have a predisposition to accumulate intracellular lipid in various tissues and organs, which alters the intracellular metabolic milieu and induces alterations in various strategic signal transduction systems, as discussed above. Such alterations induce different metabolic and physiologic alterations among individuals. In one person, obesity might result, while another may develop hypertension, non-insulin dependent diabetes mellitis (NIDDM), dyslipidemia or vascular disease depending upon specific genetic interactions. Other people might evolve symptoms based upon oxidative stress and enhanced tissue glycation, causing external signs of premature aging or memory loss. In some circumstances, the primary abnormality may be only augmented IGF effects, leading to the development of prostatic hypertrophy or frank prostate cancer in an individual.
It is desirable, therefore, to provide a means for modulating (i.e., altering or normalizing) aberrant pathways of nutrient partitioning which play a key role in numerous metabolic disorders. More particularly, it is desirable to provide a means for modulating aberrant pathways of nutrient partitioning so as to avoid excessive fat storage and excessive carbohydrate oxidation. Specifically, it is desirable to provide a means for modulating aberrant pathways of nutrient partitioning so as to promote oxidation of fat and storage of carbohydrate (glycogen).
Compositions and methods designed to reduce fat levels or otherwise improve metabolism in the body are known in the art.
A weight loss composition designed to burn and reduce synthesis of fats is disclosed, e.g., in U.S. Pat. No. 5,626,849 to Hastings et al. The composition taught in Hastings et al. contains chromium, L-carnitine, gamma-linoleic acid, (xe2x88x92) hydroxycitric acid, choline, inositol, antioxidants and herbs. The preferred antioxidants are said to be Coenzyme Q10.
U.S. Pat. No. 6,020,378 to Cook et al. discloses a method for selectively altering body fat levels in animals involving administering to the animal a combination of conjugated linoleic acid isomers in a ratio selected to retain a desirable benefit attributable to one isomer while counteracting an undesirable effect of the same isomer.
European patent application no. EP0779033 discloses an edible fat spread which is said to contribute to an improved blood lipid profile. The spread contains triglyceride fat the fatty acid residues of which includes conjugated linoleic acid (CIA) residues.
U.S. Pat. No. 5,895,652 to Giampapa discloses a method and composition which are said to supply key elements necessary for proper metabolization and function of the human body, wherein the composition includes vitamins, minerals, plant extracts, aminos, neurochemical precursors, enzymes and pH regulating agents.
U.S. Pat. No. 4,599,232 to Bertelli discloses a pharmaceutical composition for treatment of tissue energetic and metabolic disorders, wherein the composition contains carnitine or acetylcarnitine and coenzyme Q10 in ratios from 100:1 to 2:1, together with pharmaceutically acceptable excipients.
U.S. Pat. No. 5,973,004 to Howard discloses a composition for oral or parenteral administration to animals for prevention or treatment of syndromes or diseases arising from dysfunctional energy metabolism. The Howard composition includes a combination of L-carnitine and acetyl-L-carnitine, preferably with pantothenic acid or ubiquinone.
U.S. Pat. No. 6,048,846 to Cochran discloses a composition which is said to fight disease and restore the conditions of the body on a cellular level, wherein the composition contains specific and calculated quantities of hormones, amino acids, amino sugars, coenzymes, enzymes and mineral ions.
German patent no. DE 4304394A1 (abstract) discloses a composition for nourishing oncological patients, composed of fats and optionally proteins and/or carbohydrates, wherein the fat contains oleic acid, linoleic acid, alpha lipoic acid, eicosapentanoic acid and docosahexanoic acid.
WO 89/01740 discloses a composition intended for diet fortification to increase the efficiency of muscle work wherein the composition includes coenzyme Q10 as an essential component, along with nutrients, salts, vitamins, trace substances, flavorings, aromatics, etc.
None of the foregoing references is specifically concerned with the issue of altering the nutrient partitioning in the body so as to increase oxidation of fat and storage of carbohydrate (in the form of glycogen).
Accordingly, the primary object of this invention is to provide a composition and method for modulating nutrient partitioning in the body so as to increase oxidation of fat and storage of glycogen.
This object is achieved in the present invention.
The present invention is directed to a method and a nutritional supplement composition for modulating nutrient partitioning in the body so as to increase oxidation of fat and promote increased storage of glycogen. The composition of this invention is composed of effective amounts of hydroxycitric acid (HCA), carnitine, biotin, and a gluconeogenic substrate. Optionally, the composition contains one or more of the following: chromium, conjugated linoleic acid (CLA), coenzyme Q10, eicosapentaenoic acid (EPA), pyridoxine, alpha-lipoic acid, magnesium, and gymnema sylvestre. The method of this invention involves orally administering to a human on a daily basis for a therapeutically effective period of time the composition of this invention In a preferred embodiment, the method of this invention further involves following on a daily basis a dietary regimen wherein the carbohydrate content is less than about 50% of the total daily caloric intake, the glycemic index is less than about 60, and the protein content is at least about 20% of the total caloric intake. In a particularly preferred embodiment, the dietary regimen involves a multiple of small meals per day, preferably 4 to 6 meals per day. Optionally, the method of this invention further involves an exercise program and/or stress reduction program and/or blood donation program.
By modulating nutrient partitioning so as to increase oxidation of fat and promote increased storage of glycogen, the present invention promotes the normalization of macronutrient fuel partitioning pathways which contribute to or form the basis for a group of metabolic diseases. The composition and method of this invention modulate processes at the very core of each of these diseases. In so doing, the invention induces changes which are beneficially amplified at each metabolic branch point in ways designed to normalize the fundamental metabolic defect in each affected individual.
The invention also promotes accretion of lean body mass and can augment exercise performance.
With the method and composition of this invention, diminished fat synthesis and storage are accomplished coincidentally, resulting in a fall in the intracellular fat content of the liver, pancreas, and skeletal muscle as well as a fall in visceral fat and total body fat stores accompanied by a decrease in individual fat cell volume. These effects improve insulin sensitivity, decrease serum insulin levels, decrease RQ, decrease fasting serum TG and VLDL levels, decrease postprandial hyperlipidemia, downregulate cortisol production and activity, improve endothelial function, decrease the concentration of small dense LDL particles, and elevates existing low levels of HDL.
In addition, unlike other weight loss programs which reduce metabolic rate, temperature, and energy and increases hunger sensations, the present invention increases metabolic rate, temperature, and energy and decreases appetite.
Thus, with the method and composition of this invention, energy levels are elevated, appetite is suppressed, lean body mass is increased, thermogenesis is upregulated, and tendency to regain weight is diminished. These effects collectively act to prevent, reverse, or lessen the adverse metabolic diseases described herein.